Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD TG 402, EPA OPPTS 870.1200 and in accordance with the Principles of Good Laboratory Practice (GLP).
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: dark green crystalline solid
Details on test material:
- Name of test material (as cited in study report): 1,4,5,8-Tetra (4'-n-butylphenylamino) Anthraquinone (TBPAAQ)
- Substance type: dark green crystalline solid
- Physical state: solid
- Analytical purity: > 97% active ingredient
- Lot/batch No.: Lot #02080; TD No. 02-045
- Expiration date of the lot/batch: 31 March 2004
- Stability under test conditions: expected to be stable for the duration of testing
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Japan
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: males: 290 - 307 grams, females: 195 - 223 grams
- Fasting period before study: overnight fasting
- Housing: singly housed
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1°C - 27.2°C
- Humidity (%): 32.5 to 66.4%.
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Administration / exposure

Type of coverage:
occlusive
Vehicle:
corn oil
Details on dermal exposure:
One day prior to application, the fur was removed from the dorsal area of the test animals with electric clippers taking care to avoid abrading the skin. 2000 mg/kg of bodyweight of the test article was administered over an area of 2 inches by 3 inches (approximately 10% of the body surface). The test article was moistened with corn oil (Code number: CS147, Lot. 122K0131, Sigma-Aldrich) to ensure good contact with skin and applied evenly over the prepared skin with a spatula. The treatment site was covered with porous gauze held in place with a non-irritating dressing and further covered by a waterproof dressing encircling the trunk to minimize the loss of test article.

At the end of the 24 hours exposure period, the dressing was carefully removed and the treated area of skin was washed with water to remove any residual test article. Then, the treated area was blotted dry with absorbent paper. The day of application was designated as Day 1.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
5 males + 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed 1, 2, and 4 hours after application with special attention on Day 1 and at least once daily thereafter for 14 days and the body weights recorded on day 1 (prior to dosing), day 8 and day 15 (prior to necropsy).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and gross pathology
Statistics:
not applicable

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: none
Mortality:
There were no mortalities noted during the experimental period
Clinical signs:
No clinical signs of toxicity were noted during the experimental period, however, hypoactivity, vocalization immediately after applying the dressing, and nasal discharge were observed in all animals until Day 3. These signs were non-specific reactions induced by the restraint procedure during the 24-hour exposure period.
Body weight:
There was no adverse effect on the animals noted during the experimental period
Gross pathology:
No macroscopic abnormalities were detected at necropsy
Other findings:
The clinical signs of bluish to greenish discoloration of the skin at the treatment sites of all the animals was observed between Day 2 and Day 8. This sign was considered to be related to the dark green color of the test article and not an indication of toxicity.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the single dose acute dermal LDS0 of the active ingredient in 1,4,5,8-Tetra(4'-n-butylphenylamino)anthraquinone (TBPAAQ) is greater than 2000 mg/kg of bodyweight in male and female rats and hence will not be classified.
Executive summary:

The purpose of this study was to assess the acute toxicity of 1, 4, 5, 8-Tetra (4'-nbutylphenylamino) anthraquinone (TBPAAQ), following a single exposure by the dermal route in rats.

One group of five male and five female [Crj:CD®(SD)IGS BR strain] rats received the test article at the limit dose level of 2000 mg/kg of the active ingredient. Assessment of toxicity was based on mortality, clinical observations, bodyweight changes, and gross necropsy findings.

All animals survived until the scheduled sacrifice. There were no treatment-related adverse effects observed in clinical signs or bodyweight changes. No gross necropsy findings indicative of test article effects were observed at study termination. Observations of bluish to greenish discoloration of the skin at the treatment sites of all animals were considered to be related to the dark green color of the test article.

Under the conditions of this study, the single dose acute dermal LD50 of the active ingredient in 1, 4, 5, 8-Tetra (4'-n-butylphenylamino) anthraquinone (TBPAAQ) is greater than 2000 mg/kg of body weight in male and female rats and hence will not be classified.